Striated muscle in Duchenne dystrophy is characterized by an extensive interstitial fibrosis. Although formerly considered as a replacement phenomena, structural, biochemical and tissue culture studies suggest that the increase in connective tissue (CT) matrix may play an active or even primary role in dystrophic degeneration. The aim of the proposed study is to analyze the origin and influence of CT in the progression of Duchenne dystrophy. Clonal cultures of normal and dystrophic myoblasts and fibroblasts will be examined for their ability to synthesize endomysial and perimysial CT. In addition to quantitative collagen assays, development of the CT matrix will be evaluated on the light and EM levels. Results of these analyses will provide evidence as to whether a defect in CT biogensis exists in dystrophic cells. It is hyypothesized that an increased CT matrix in dystrophic muscle could create an ischemia by acting as a barrier between myofibers and their feeding capillaries. The investigation of a possible vascular defect would include a structural analysis of CT organization and its relationship to blood vessels and muscle cells in human muscular dystrophy. An experimental study concerned with the dynamic aspects of a possible ischemia will include radioautographic and EM examinations of the transport of labelled compounds between vessels and muscle fibers in dystrophic animals. A proposed myoblast-fibroblast transformation may account for the progressive pathogenesis observed in muscular dystrophy. Presumed "transformed" myoblasts, induced in muscle clones subjected to adverse conditions simulating ischemia, will be assayed for their ability to synthesize CT components.